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Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma associated with hemophagocytic lymphohistiocytosis (HLH)/HLH-like systemic illnesses and germline HAVCR2 mutations. Although previous studies suggested successful treatment of SPTCL with immunosuppressive therapy (IST) without chemotherapy, IST data in pediatric SPTCL remain scarce. To explore characteristics and therapeutic outcomes, comparing IST-based and chemotherapy-based regimens in pediatric SPTCL, in this retrospective cohort study, patients with SPTCL diagnosed at age ≤20 years during 2007-2023 were enrolled from 6 hematology/oncology centers in Thailand. HAVCR2 exon 2 sequencing was performed using DNA extracted from peripheral blood or bone marrow. Presence of HLH/HLH-like systemic illnesses, treatment outcomes, and adverse events (AEs) were reviewed and analyzed., Results: Of 22 patients with SPTCL (median age at diagnosis, 11.5 years [range, 6.0-19.0]; 63.6% males), 86.4% harbored germline HAVCR2 mutation, either homozygous (77.3%) or heterozygous (9.1%) p.Y82C variant, while 68.2% developed HLH/HLH-like systemic illnesses. Overall, 36.4% received IST as first-line treatment. Durable complete remission (CR) was achieved in 71.4% and 50.0% after first-line chemotherapy and IST, respectively (P=0.45); however, chemotherapy tended to increase any AEs compared to IST (57.1% vs. 12.5%; P=0.07). The most common AEs were hypertension (27.3%), febrile neutropenia (18.2%), and fungal infection (13.6%). Among the relapsed cases, 71.4% could reach CR after subsequent-line therapy. Fatality (4.5%) only occurred in the chemotherapy group., Conclusions: Pediatric SPTCL in Thailand frequently involves germline HAVCR2 mutations and/or HLH/HLH-like systemic illnesses. With comparable response and modest therapy-related toxicity, IST-based regimens may alternatively be considered as first-line treatment for pediatric SPTCL., Competing Interests: Declarations Ethical approval and consent to participate The study protocol was ethically approved by the Institutional Review Boards of all the study sites, including the central study site at the Faculty of Medicine, Chulalongkorn University (IRB no. 0607/65). Written informed consent forms were obtained from each patient and/or their parents/guardians prior to participation in the study, in accordance with the Declaration of Helsinki. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral T-cell lymphoma characterized by cutaneous lesions and immunologic manifestations. The five-year survival rate of SPTCL has been reported to be over 80%, indicating a favorable prognosis. Recent studies have uncovered recurrent germline variants in HAVCR2, encoding an immunomodulator. In this study, we integrated whole-exome sequencing data from 60 samples collected from 36 SPTCL patients, encompassing six patients of our cohort and 30 patients of publicly available data. We identified 138 somatic mutations in skin tumors of 24 patients and HAVCR2 germline mutations in 23 of 29 patients. HAVCR2 p.Tyr82Cys mutations were identified in four of six Japanese patients. During the clinical courses of four patients, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone were administered to all patients, but it resulted in incomplete responses in all four patients. However, disease conditions of all patients remained stable with additional treatment, including autologous peripheral blood stem cell transplantation. Over a 7.5-year median follow-up, one patient developed autoimmune-related diseases, while one developed other hematological malignancy, resulting in death. To our knowledge, this is the first report of recurrent HAVCR2 germline mutations in Japanese patients, suggesting the necessity for long-term follow-up., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A 10-y-old spayed female Cavalier King Charles Spaniel dog was presented to the Veterinary Teaching Hospital because of recurrent chronic abscesses on the distal pelvic limbs, fever, lethargy, lameness of unknown etiology, and chronic pancreatitis. Sterile nodular panniculitis was diagnosed after an extensive workup, and the dog initially responded to immunosuppressive therapy, but relapse and spread of cutaneous lesions and acute lameness occurred after 11 mo, and euthanasia was elected. Postmortem examination confirmed hyalinizing pancreatic adenocarcinoma with pancreatitis, panniculitis, polyarthritis (PPP), and osteomyelitis. Histopathology and bacterial and fungal cultures were supportive of a sterile process, specifically the PPP syndrome, which is a rare, potentially life-threatening, systemic manifestation of pancreatic disease in both people and animals. To our knowledge, a clinicopathologic description of a hyalinizing pancreatic adenocarcinoma associated with this rare syndrome has not been reported previously in a dog., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Mpox, previously referred to as monkeypox, was recently deemed a public health emergency in 2022. Our understanding of potential secondary cutaneous manifestations in the setting of this infection is still evolving. We report a rare case of a man who presented with erythematous, painful subcutaneous nodules on his extremities in the setting of recent mpox infection. Biopsy of a lesion from the lower legs revealed a lobular panniculitis with lupus panniculitis-like features on pathology. He was ultimately diagnosed with a unique case of reactive panniculitis secondary to mpox., Competing Interests: M. S. Min is on the advisory boards of Horizon and BMS and an investigator for Amgen, BMS, BI, and Priovant. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Acquired generalized lipodystrophy (AGL) is a rare disease characterized by variable loss of adipose tissue and concurrent metabolic derangements, typically with childhood or adolescent onset. AGL has three subclassifications: panniculitis (type 1), autoimmune disease (type 2), and idiopathic (type 3). This report highlights a rare case of AGL type 1 in a previously healthy 3-year-old female who presented with diffuse erythematous subcutaneous nodules, progressive lipoatrophy, and histopathological findings of a lobular panniculitis., (© 2024 Wiley Periodicals LLC.)

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of non-Hodgkin lymphoma that primarily affects subcutaneous tissues. Its occurrence in the orofacial region is exceptionally uncommon, presenting diagnostic challenges due to symptom overlap with more prevalent orofacial condition., Case Presentation: This report details the case of a 15-year-old male who presented with persistent left-sided facial swelling, initially misdiagnosed as facial cellulitis. Diagnostic complexity arose from the similarity of symptoms to common orofacial diseases. Comprehensive diagnostic approaches, including liquid-based thin-layer cytometry, immunohistochemistry, and advanced imaging, were pivotal in identifying SPTCL. The recurrence of symptoms following the cessation of dexamethasone treatment indicated hormone dependency. Surgical intervention and subsequent histopathological analysis confirmed SPTCL, with immunohistochemical profiling playing a critical role in the definitive diagnosis. The patient's management involved a multidisciplinary approach, leading to a referral to a hematology specialist and subsequent favorable outcomes., Conclusions: This case underscores the diagnostic challenges of orofacial lymphomas such as SPTCL and highlights the necessity for early, accurate pathological diagnosis. It emphasizes the role of advanced diagnostic techniques and the importance of a comprehensive, multidisciplinary approach in the management of such rare cases. This report contributes to the limited but growing body of literature on SPTCL in the orofacial region, providing insights for clinicians in similar future cases., (© 2024. The Author(s).)

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Due to its rarity, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is often misdiagnosed as benign panniculitis, and there are no standardized treatment guidelines for SPTCL. Aurora kinase A (AURKA) plays a regulatory role in both mitosis and meiosis. Cells treated with an AURKA inhibitor showed severe mitotic delay, which triggered apoptosis., Materials and Methods: Ten cases of SPTCL were collected in this study, and immunohistochemistry was performed to detect AURKA expression in the skin tissues of these cases. Control groups were set as follows: 1) 10 cases of inflammatory panniculitis; 2) 9 healthy individuals. Fisher's exact test was used to compare the positive rates of AURKA among various groups., Results: An average onset age of 27.3 years was found in 10 SPTCL cases. Clinically, these patients primarily presented with multiple subcutaneous nodules on the trunk and lower extremities, accompanied by intermittent high fever. One case showed lymph node metastasis, while no other distant organ metastasis being observed in any case. Pathologically, there was an infiltration of a large number of atypical lymphocytes within the fat lobules, characterized as a cytotoxic type. AURKA stanning was positive in 6 out of 10 SPTCL cases, while no positive cases were found in the control groups., Conclusion: 1) SPTCL predominantly affects young individuals and can be identified by nodular erythema on the trunk, intermittent high fever, and infiltration of atypical cytotoxic lymphocytes within fat lobules. 2) For early-stage cases without metastasis, monotherapy with glucocorticoids or immunosuppressants such as cyclosporine can be considered. 3) High expression of AURKA in SPTCL tissues suggests that AURKA could be a potential biomarker for disease diagnosis, providing a theoretical basis for further targeted therapy., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Abstract: A 65-year-old woman presented with unexplained weight loss, recurrent fever, and a dermatosis with painful nodules on the extremities. Biopsies showed focal lobular panniculitis with neutrophilic microgranulomas. Comprehensive investigations ruled out infection and hematologic and solid organ neoplasms. Laboratory results showed anti-Ro/SSA and anti-La/SSB antibody positivity, and elevated inflammatory markers. Dry mouth and eye were confirmed. The diagnosis of Sjögren syndrome with cutaneous panniculitis was established. Prednisone treatment with 30 mg/d resulted in remission of fever and pain improvement. This case emphasizes Sjögren syndrome as an autoimmune disease with multiple cutaneous manifestations and highlights its association with granulomatous panniculitis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Background: The occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) may be due to HAVCR2 gene mutation, leading to T-cell immunoglobulin and mucin domain-containing molecule 3 deficiency, T-cell and macrophage activation, and proinflammatory cytokine production., Observation: We report a patient with SPTCL and HLH for whom ruxolitinib, used as a novel treatment, showed notable therapeutic effects., Conclusions: Remission of both HAVCR2 mutation-induced high inflammatory characteristics and significant symptoms post-ruxolitinib administration suggested that patients with SPTCL and HLH may not represent typical lymphoma cases. Ruxolitinib, with its relatively low toxic side effects, can provide favorable outcomes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Erythema nodosum (EN) may be idiopathic or secondary, and usually resolves naturally within 1-2 months. In atypical EN cases, the rash extends beyond the lower limbs to the upper limbs and trunk, and histopathological findings may be accompanied by vasculitis in addition to septal panniculitis. Few studies have examined the differences in the clinical characteristics of patients with EN based on rash distribution. We retrospectively examined whether there was a correlation with clinical information, such as the presence or absence of underlying diseases, by classifying the patients into two groups: the lower limbs group (the EN rash was confined to the lower limbs) and the beyond lower limbs group (the EN rash appeared beyond the lower limbs). Among the 86 adult patients diagnosed with EN at the Dermatology Department of Fujita Medical University between 2015 and 2020, there were 65 cases of the lower limbs group and 21 cases of the beyond lower limbs group. The frequency of underlying diseases was significantly higher in the beyond lower limbs group (76.2%, 16 cases) than in the lower limbs group (40.0%, 26 cases; P < 0.005). Vasculitis was more notable in the beyond lower limbs group (P < 0.05). Significantly higher vasculitis was noted in the EN group with underlying diseases (30.2%, 13 cases) than in the idiopathic EN group without underlying diseases (11.6%, 5 cases; P < 0.05). Neutrophil extracellular traps were positive in approximately 40% of cases in both groups. In the beyond lower limbs group, the possibility of severe cases with underlying diseases, vasculitis, and inflammation must be considered for effective treatment., (© 2024 Japanese Dermatological Association.)

A white Caucasian woman in her 30s presented with an indurated lesion on her right upper arm. Panniculitis was clinically suspected. Antinuclear antibody testing was positive but incisional biopsy showed subcutaneous panniculitis-like T-cell lymphoma (SPTCL), although with some unusual features more in keeping with lupus. Initial treatment was with oral prednisolone and radiotherapy but with only partial response. A second biopsy was taken from an area of presumed residual disease. This displayed histological features that were much more typical of lupus erythematosus profundus (LEP) but with tiny foci suggesting concomitant microscopic areas of SPTCL. Immunofluorescence for IgM was positive. This case highlights the rare occurrence of a patient with overlapping clinical and pathological features of SCPTL and LEP. It emphasises the need for close clinicopathological correlation in the workup of patients with suspected panniculitis and the importance of careful pathological examination for features of both diseases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis.

Abstract: Gamma/delta T-cell lymphoma is a rare and aggressive subtype of primary cutaneous lymphoma. Clinical manifestations typically include the development of subcutaneous nodules and ulcerated plaques. Some forms present as panniculitis with hemophagocytic syndrome. Prognosis is bleak, with a 10% 5-year survival rate. In this report, we present the case of a 20-year-old man from French Polynesia, referred for 18 F-FDG PET/CT because of the progressive worsening of febrile cutaneous-mucosal infiltration on the face persisting for 1 month. PET examination guided a biopsy from the right deltoid muscle, and expert histological analysis confirmed a CD8 + not otherwise specified T-cell lymphoma, granzyme+ and TCR gamma/delta., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Subcutaneous fat necrosis of the newborn (SCFN) is a rare form of panniculitis manifesting as erythematous plaques or nodules at sites of brown fat in neonates. Surgical management may be indicated in severe cases; however, there is a paucity of literature compiling presentations and outcomes of these surgical patients., Methods: The authors performed a systematic review, in consultation with a licensed librarian, on MEDLINE and Embase for studies including patients with SCFN who were surgically managed., Results: The search strategy generated 705 results, among which 213 (30.2%) were excluded for lack of discussion on surgical management. Twenty-two studies discussed surgical management of SCFN in 26 patients, but in 6 of these studies the patients were not surgically managed. Ultimately, 16 articles with 16 patients who were surgically managed were included in the study. Average age at diagnosis was 11.8 ± 9.8 days; average age at surgery was 39.5 ± 70.4 days. The most common etiologies were "unknown" (6, 37.5%), therapeutic hypothermia (4, 25.0%), and birth complications (4, 25.0%). Patients harbored nodules on the back (14, 87.5%), upper extremities (7, 43.8%), lower extremities (7, 43.8%), buttocks (5, 31.3%), and head or neck (3, 18.8%). Linear regression models revealed the presence of back lesions and predicted concomitant medical complications (β = 2.71, p = 0.021)., Conclusions: Patients undergoing surgical management for SCFN most commonly harbor lesions on the back and extremities that are secondary to therapeutic hypothermia or of unknown origin. Reporting of additional cases is needed to further elucidate surgical management and outcomes., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Panniculitis was first described in the nineteenth century and is characterized by inflammation of the subcutaneous fat. It may be categorized in septal or lobular subtypes, but other histopathological features (e.g., presence of vasculitis, nature of inflammatory infiltrates, characteristics of fat necrosis) are also important for diagnostic purposes. Clinically, panniculitis is characterized by the presence of subcutaneous nodules, and both ulcerative and nonulcerative clinical subtypes have been proposed. In this review, we aimed to describe the occurrence of panniculitis in autoinflammatory disorders (AIDs) and related diseases. Among monogenic AIDs, panniculitis is common in IFN-mediated disorders. Panniculitis is a distinctive feature in proteasome-associated autoinflammatory syndromes (PRAAS), including chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and Nakajo-Nishimura syndrome. On the other hand, erythema nodosum corresponds to the most common clinical form of panniculitis and is common in polygenic AIDs, such as Behçet's syndrome, inflammatory bowel disease, and sarcoidosis. Cytophagic histiocytic panniculitis, lipoatrophic panniculitis of children, and otulipenia are rare disorders that may also present with inflammation of the subcutaneous fat. Therefore, panniculitis can identify a specific subgroup of patients with AIDs and may potentially be regarded as a cardinal sign of autoinflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Erythema nodosum (EN) is the most common form of panniculitis that predominantly affects the shins. While EN in atypical sites has been described by many authors, there are currently only case studies published on this topic. This study aimed to evaluate clinical differences between patients suffering from EN on the shins, compared to patients with EN in atypical locations., Methods: We analyzed 105 patients in a retrospective, single-center study at a university hospital in Switzerland. Typical EN was defined as lesions, found only on the lower legs, while atypical EN as lesions on the upper legs, trunk, arms, or face, only or in addition to lesions on the lower legs. The patients were assessed for age, gender, dermatologic history, time until first medical consultation, time to diagnosis, and time until remission. Further, etiology, symptoms, and applied therapies were investigated. Findings were then compared between the typical and atypical EN cohorts., Results: Overall, we included 70 patients (37.99 ± 15.67 [3-81] years) with EN solely on the shins and 35 patients (41.27 ± 16.85 [9-76] years) with EN on other locations. Interestingly, time until diagnosis was significantly shorter in atypical EN (p = 0.034, 1.14 ± 4.68 vs. 0.46 ± 1.14 months). Time to remission was similar in both groups (3.61 ± 2.73 vs. 3.05 ± 2.86 months, respectively). Sarcoidosis was the only etiologic factor significantly more frequent in atypical EN compared to typical EN (23% vs. 9%, p = 0.042). Besides that, solely subtle differences were seen regarding etiology, gender, age at onset, course of the disease, and symptoms., Conclusions: Our study suggests that only minor alterations between both study populations exist. Significant differences were found in time to diagnosis (shorter for atypical EN), as well as in sarcoidosis as an etiologic factor (more frequent in atypical EN). While adalimumab was only prescribed in atypical EN cases, prognosis seems to be similar for typical and atypical EN (similar time to remission, similar amount of reoccurring cases). Due to the limited sample size, however, our study population may have been too small to detect the relevant differences, and bigger studies may be needed., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Discoid lupus erythematosus (DLE), a subtype of chronic cutaneous lupus may be observed in a linear pattern. A 21-year-old woman with history of chronic granulomatous disease state presented to our clinic for a chronic six-year skin eruption on her left eyebrow, left cheek, and left forehead. A punch biopsy of involved left forehead skin was performed and revealed perivascular and periadnexal lymphohistiocytic infiltrate without features of morphea or panniculitis, confirming the histopathologic changes of cutaneous lupus erythematous. The patient was diagnosed with linear DLE, mimicking en coup de sabre, within Blaschko lines. The pathogenesis for DLE in association with chronic granulomatous disease is ambiguous; however, X-linked lyonization is crucial for both conditions and may explain cooccurrence of disease states.

Pancreatic panniculitis is an uncommon manifestation of pancreatic disease, affecting approximately 2-3% of patients with acute or chronic pancreatitis [1]. Its accurate diagnosis is crucial for effective treatment as skin manifestations usually precede systemic symptoms of pancreatitis. The diagnosis of pancreatic panniculitis requires identifying and confirming pancreatic disease in addition to the typical histopathological findings of lobular panniculitis without vasculitis. Herein, we present a patient with pancreatic panniculitis, underlying acute pancreatic failure, and kidney injury.

Distinguishing lupus erythematosus panniculitis (LEP) from subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a diagnostic challenge with important clinical implications. Immunohistochemical expression of interferon regulatory factor 8 (IRF8) has been shown to highlight cells with plasmacytoid dendritic cell differentiation. Considering that the presence of plasmacytoid dendritic cells highlighted by CD123 immunolabeling is a well-described feature that supports LEP over SPTCL, we hypothesized that IRF8 immunohistochemistry can be used as a diagnostic test to improve accuracy in differentiating LEP from SPTCL. In this study, we assessed the expression of IRF8, CD123, and CD20 in 35 cutaneous biopsies from 31 distinct patients, which included 22 cases of LEP and 13 cases of SPTCL. We found that clusters of IRF8-positive cells within the dermis, and away from subcutaneous fat, could discriminate LEP from SPTCL ( P =0.005). Similarly, CD123-positive clusters in any location were observed in LEP but absent in all cases of SPTCL. In addition, we found that dermal CD20-predominant lymphoid aggregates could help discriminate LEP from SPTCL ( P =0.022). As individual assays, IRF8, CD123, and CD20 were highly specific (100%, 100%, and 92%, respectively) though poorly sensitive (45%, 29%, and 50%, respectively). However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL., Competing Interests: Conflicts of Interest and Source of Funding: M.L.X. discloses consultancy for Seattle Genetics, Pure Marrow, and Blueprint Medicines that is unrelated to this study. For the remaining authors none were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Wang, Zhang, Hu, Wu and Wang.)

We herein report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) resembling adult-onset Still's disease (AOSD). A 40-year-old woman presented with a fever, erythema, and painful subcutaneous nodules on the trunk. Laboratory data and a bone marrow analysis showed hemophagocytic syndrome. Although AOSD was suspected, based on a histopathological evaluation of the erythema, she was diagnosed with SPTCL. She was refractory to combination chemotherapy but achieved durable remission with cyclosporine monotherapy. Genetic testing revealed a homozygous HAVCR2 c.245A>G variant (rs184868814) that had caused NLRP3 inflammasome activation. SPTCL and AOSD share a pathogenesis in terms of NLRP3 inflammasome activation, so the clinical phenotype of SPTCL reasonably mimics AOSD.

The skin covers the external surface of animals, and it is constantly exposed to and inhabited by different microorganisms, including bacteria. Alterations in the skin barrier allow commensal and/or pathogenic bacteria to proliferate and penetrate deep into the lower layers of the skin. Being the first barrier to the external environment, the skin is prone to injuries, allowing the penetration of microorganisms that may lead to severe deep infections. Companion animals, especially dogs, are prone to bacterial infections, often secondary to allergic dermatitis. When environmental conditions are unfavorable, horses, cattle, sheep, and goats can develop superficial infections, such as those caused by Dermatophilus congolensis . Deep inflammation is commonly caused by Mycobacterium spp., which results in granulomatous to pyogranulomatous dermatitis and panniculitis. Likewise, bacteria such as Nocardia spp. and Actinomyces spp. can cause deep pyogranulomatous inflammation. Bacteria that lead to deep necrotizing lesions (eg, necrotizing fasciitis/flesh-eating bacteria) can be severe and even result in death. This review includes an overview of the most common cutaneous bacterial infections of domestic animals, highlighting the main features and histologic morphology of the bacteria, cutaneous structures involved, and the type of inflammatory infiltrates., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pancreatic panniculitis is a rare cutaneous manifestation of pancreatic disease with only scant case reports available to guide management. In this report, a woman in her 60s developed a painful, erythematous and indurated, nodular rash after an episode of acute pancreatitis postendoscopic retrograde cholangiopancreatography (ERCP). While clinically and radiologically the pancreatitis improved with standard conservative management, the panniculitis remained severely debilitating. Repeat testing of serum pancreatic enzymes revealed persistent and marked elevation. Octreotide was started to inhibit pancreatic enzyme release, and the lesions improved, with resolution of the panniculitis correlating with falling serum pancreatic enzyme levels. Hence, serial pancreatic enzyme testing may have utility in monitoring and management of pancreatic panniculitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous non-Hodgkin lymphoma involving CD8 + T cells, the genetic underpinnings of which remain incompletely understood. Here we report two unrelated patients with B cell Expansion with NF-κB and T cell Anergy (BENTA) disease and a novel presentation of SPTCL. Patient 1 presented early in life with recurrent infections and B cell lymphocytosis, linked to a novel gain-of-function (GOF) CARD11 mutation (p.Lys238del). He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine. Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. Genetic analysis revealed two in cis germline GOF CARD11 variants (p.Glu121Asp/p.Gly126Ser). Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4 + and CD8 + T cell malignancies., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.

Progressive crossed hemiatrophy is an extremely rare clinical type of facial hemiatrophy that presents primarily as unilateral facial atrophy and contralateral trunk or limb involvement. The undistinguishable clinical manifestation and pathological changes complicate diagnosis, especially at the onset of the disease when presenting with less clinical evidence. Here, we report a case of a 9-year-old boy started with left scalp induration, following with subcutaneous tissues atrophy on the right trunk. He was mistaken as panniculitis based on the pathologic findings and treated with topical tacrolimus without any improvement. Immune-related tests were implemented to exclude connective tissues. Imaging examinations such as magnetic resonance was conducted to evaluate the range and degree of the involvement of the skin, soft tissue, and cranial changes. Although no effective treatment to hold back the progress has been reported so far, surgeries might work to restore the appearance to some extent or improve central nerves symptoms if they exist., (© 2023 Japanese Dermatological Association.)

Mature T- and NK-cell neoplasms (MTNKN) collectively represent a rare disorder, representing less than 15% of all non-Hodgkin lymphoma (NHL) cases and qualifying for orphan disease designation by the U.S. Food and Drug Administration (FDA). These consist of 9 families in the fifth revised WHO classification of lymphoid neoplasms, which are made up of over 30 disease subtypes, underscoring the heterogeneity of clinical features, molecular biology, and genetics across this disease group. Moreover, the 5 most common subtypes (peripheral T-cell lymphoma, not otherwise specified; nodal TFH cell lymphoma, angioimmunoblastic type; extranodal NK-cell/T-cell lymphoma; adult T-cell leukemia/lymphoma; and ALK-positive or -negative anaplastic large cell lymphoma) comprise over 75% of MTNKN cases, so other subtypes are exceedingly rare in the context of all NHL diagnoses and consequently often lack consensus on best practices in diagnosis and management. In this review, we discuss the following entities-enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and primary cutaneous ɣδ T-cell lymphoma (PCGD-TCL) - with an emphasis on clinical and diagnostic features and options for management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disease with frequent cutaneous manifestations., Methods: We conducted a retrospective study of all patients with genetically confirmed VEXAS syndrome seen at our institution. Available clinical photographs and skin biopsy slides were reviewed., Results: Cutaneous manifestations developed in 22/25 (88%) patients with VEXAS syndrome. From this group, 10/22 (45%) developed skin involvement before or at the time of other clinical features of VEXAS. Twenty distinct dermatologic presentations of VEXAS from 14 patients were reviewed, and histopathologic patterns were classified as follows: neutrophilic urticarial dermatosis (n = 5, 25%), leukocytoclastic/urticarial vasculitis (n = 4, 20%), urticarial tissue reaction (n = 4, 20%), neutrophilic dermatosis (n = 3, 15%), neutrophilic panniculitis (n = 2, 10%), and nonspecific chronic septal panniculitis (n = 2, 10%). Common systemic findings included macrocytic anemia (96%), fever (88%), thrombocytopenia (76%), weight loss (76%), ocular inflammation (64%), pulmonary infiltrates (56%), deep venous thrombosis or pulmonary embolism (52%), and inflammatory arthritis (52%)., Conclusions: Cutaneous involvement is a common feature of VEXAS syndrome, and histopathologic findings exist on a spectrum of neutrophilic inflammatory dermatoses., (© 2023 the International Society of Dermatology.)

Purpose: Even though subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus panniculitis (LEP) are two separate entities, recently they were claimed to represent two ends of a spectrum of T-cell-mediated orbital lymphoproliferative diseases., Methods: A 78-year-old woman presented with a 1-month history of right-sided periorbital swelling and redness. There was a palpable mass in the medial right lower eyelid with restriction of upward and lateral gaze. MRI revealed a 14 × 7 mm hypointense lesion in the anteromedial orbit., Results: The systemic and ocular findings, orbital biopsy with histopathology and immunochemistry showed overlapping features of LEP and SPTCL. The patient was consulted with rheumatology and hematology, and the physicians arrived at a consensus that the patient existed in the above-mentioned disease spectrum. She was started on systemic immunosuppressive treatment and her clinical findings improved substantially., Conclusions: This is the first report of a patient, who presented with orbital mass causing vision loss and gaze restriction that had overlapping clinical and histopathologic features of LEP and SPTCL consistent with this novel disease spectrum, in the literature.

Introduction: Pancreatic panniculitis is a rare skin manifestation of pancreatic disease. It is characterized by inflammation and liquefactive necrosis of subcutaneous fat. Treatment involves addressing the underlying cause and providing supportive wound care., Case Report: The authors present a case of a 68-year-old man who developed painful, erythematous wounds on his lower extremities that progressed to purple, edematous lesions with purulent drainage. During the progression of his wounds, he developed epigastric pain and acute pancreatitis. Subsequent CT scan showed a pancreatic cyst that had extended into the portal vein. Deep, excisional biopsy of the wounds helped further narrow the differential. Histology indicated "ghost cells," which are adipocytes with a central clearing and dark basophilic calcium deposits in the cytoplasm., Conclusion: The presence of ghost adipocytes is a rather unique histopathological feature consistent with pancreatic panniculitis and should be considered in combination with the overall clinical picture to determine the underlying etiology. Pancreatic panniculitis can be a primary presenting feature and possible complication of pancreatic disease.

Subcutaneous fat necrosis of the newborn is a rare self-limited panniculitis that classically presents within the first few weeks of life. The diagnosis is typically clinical, but some cases require skin biopsy with hematoxylin and eosin stain for confirmation. We report a previously undocumented rapid diagnostic protocol that involves collecting a small amount of exudate from a suppurative lesion, placement onto a slide without fixation, and simply viewing the material under a microscope. This novel and practical method of diagnosis reveals doubly refractile crystals diagnostic of subcutaneous fat necrosis without a biopsy, which may be helpful for rapid diagnosis or use in low resource settings., (© 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Abstract: A 47-year-old woman presented with a 2-month history of subcutaneous nodules, erythema, and fever. 18F-FDG PET images demonstrated inverted FDG uptake pattern corresponding to the subcutaneous lesion against lymph nodes. The specimen of the inguinal lesion showed massive infiltration of small lymphocytes in the adipose tissue with rimming adipocytes, whereas very few tumor cells infiltrated the lymph nodes. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed. SPTCL normally shows quite interesting distribution of tumor cells, that is, lymph node involvement is usually absent. Therefore, this case highlighted the importance of the inverted accumulation pattern on FDG PET to suspect SPTCL., Competing Interests: Conflicts of interest and sources of funding: The authors have no conflicts of interest. The present study was financially supported by JSPS KAKENHI (grant number 22K15879)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this systematic review is to investigate different diagnostic methods and the available treatment options for subcutaneous panniculitis-like T-cell lymphoma (SPTCL)., Methods: We searched PubMed, Web of Science, SCOPUS, EBSCO, and CINAHL Plus for published case reports of SPTCL. From each record, we extracted data of the diagnostic methods, immunohistochemical profile, clinical characteristics, and the treatment approaches provided. Data were summarized and narratively synthesized to highlight the various diagnostic methods and treatment options of SPTCL., Results: Our literature search yielded 1293 unique citations. Following screening, nine articles reporting a total of 15 cases were included in this systematic review. All patients presented with subcutaneous nodules. Three of the 15 cases were initially misdiagnosed. The atypical lymphoid cells were positive for CD2, CD3, granzyme B, and TIA-1 and negative for CD1a, EBER, and CD20 in all the reported cases. The atypical lymphoid cells were positive for CD45RO in four out of seven cases, positive for CD56 in three out of 12 cases tested, while positive for CD5 and CD8 in the majority of cases. Therapy ranged from topical agents to immunosuppressive agents all the way to multiagent chemotherapy., Conclusion: SPTCL is a rare lymphoma. Diagnosis is highly dependent on the immunohistochemical stains added to histopathologic and radiologic findings. Therapy is dependent on the pace of the disease, with encouraging results obtained with single-agent cyclosporine.

Pancreatic acinar cell carcinoma is a rare type of pancreatic malignancy, which can be confused with pancreatic neuroendocrine neoplasm. Here, we describe a woman in her 80s who presented with abdominal pain and bilateral lower extremity panniculitis. She underwent surgery for a presumed diagnosis of neuroendocrine tumour with PTEN and PRKAR1A alterations; 19 months, later, a recurrence of her pancreatic malignancy was discovered. The patient underwent repeat resection and this time immunohistochemical staining confirmed the diagnosis of acinar cell carcinoma. Staining for acinar cell carcinoma should be prompted based on clinical suspicion in context of PTEN or PRKAR1A mutation when appropriate., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare, cytotoxic T-cell lymphoma with which some patients have accompanying hemophagocytic syndrome (HPS). There is currently no standard treatment regimen. In the past, the most commonly used treatment was multidrug chemotherapy. In contrast, numerous case reports or small series suggest that immunosuppressive drugs could also be effective for some patients. Since this NHL subtype is extremely rare in children and adolescents, to improve the understanding of this disease and standardize its rational treatment, we retrospectively summarized the treatment regimens of 18 pathologically diagnosed children with SPTCL to compare the clinical efficacy of multidrug chemotherapy and immunomodulatory therapy., Results: The median age of onset was 11.1 years. Painless subcutaneous nodules or skin patchy lesions were found in all patients, most commonly involving the lower extremities and/or trunk. Before January 1, 2019, the treatment was mainly chemotherapy, and 10 patients were initially treated with chemotherapy, among whom was one patient who progressed during initial treatment, was voluntarily discharged and was subsequently lost to follow-up, one patient who died of disease progression, and the remaining 8 patients who all achieved sustained remission, with a complete remission (CR) rate of 80% (8/10). Corticosteroids combined with cyclosporine A or ruxolitinib were the most common initial immunosuppressive agents at our center after January 1, 2019 and had a CR rate of 71.4% (5/7). In addition, 1 patient achieved partial remission (PR) during follow-up, and one had autologous hematopoietic stem cell transplantation (AHSCT) after 4 months of drug withdrawal. There were 7 patients (38.9%, one case in chemotherapy group and six cases in immunotherapy group) with HPS and 4/5 screened patients (80%) with positive HAVCR2 gene mutations. The median follow-up was 17 months., Conclusion: The prognosis of SPTCL is relatively good. Previous multi-drug and long-term chemotherapy treatment has clear efficacy, and recent immunomodulatory therapy as pre-chemotherapy therapy can also benefit patients., (© 2022. The Author(s).)